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Pharmacol Res. 2018 Oct 29. pii: S1043-6618(18)31201-5. doi: 10.1016/j.phrs.2018.10.025. [Epub ahead of print] The Emergence of loss of efficacy during Antidepressant Drug Treatment for Major Depressive Disorder: An Integrative Review of Evidence, Mechanisms, and Clinical Implications. Fornaro M1, Anastasia A2, Novello S3, Fusco A4, Pariano R5, De Berardis D6, Solmi M7, Veronese N8, Stubbs B9, Vieta E10, Berk M11, de Bartolomeis A12, Carvalho AF13. Abstract at https://www.ncbi.nlm.nih.gov/pubmed/30385364 The re-emergence (i.e. 'breakthrough') of depressive symptoms despite maintenance treatment of depression with antidepressant drugs is a complex clinical phenomenon referred to as tolerance. Herein we critically appraise evidence from both pre-clinical and clinical studies, focusing on putative mechanisms as well as clinical correlates and implications of the emergence tolerance during antidepressant treatment for major depressive disorder (MDD). It is firstly unclear to what extent this phenotype reflects a pharmacological effect of an antidepressant, is driven by non-adherence, is a marker of latent bipolarity or another comorbidity, a marker of neuroprogression of the underlying disorder or the intrusion of the impact of psychosocial variables into the clinical course. The operational definitions of tolerance and its related phenomena have also been largely inconsistent. Several protective clinical indicators have been proposed, including a rapid-cycling course and comorbid chronic anxiety, whilst poor treatment adherence, proneness to emotional blunting and sub-threshold bipolarity have been identified as possible correlates of tolerance to antidepressant treatment in MDD. Putative neurobiological underpinnings include adaptations in the hypothalamic-pituitary-adrenal (HPA) axis and the serotonergic system. Due to the clinical and diagnostic challenges imposed by the emergence of tolerance to antidepressants, there is an urgent need for upcoming international guidelines to reach a consensus on operational definitions for this complex clinical phenomenon, thus enabling a more precise appreciation of the incidence and correlates of tolerance to antidepressants. Taken together, the present review underscores the need to cautiously weight benefits and risks prior to considering long-term antidepressant treatment for patients with MDD as tolerance may emerge in a subset of patients.
From: verywell.com What is "Prozac poop-out"? If it seems like your Prozac (or another SSRI such as Zoloft, Paxil, or Celexa) stopped working, why might that be, and what can you do? What Exactly is Prozac Poop-Out? When we talk about the phenomenon of Prozac (fluoxetine) poop-out, what we mean is that a person's antidepressant has simply stopped working as well as it once did, causing a relapse of depression symptoms. Although this phenomenon is most commonly referred to as "Prozac poop-out," it can actually occur with any SSRI. An selective serotonin reuptake inhibitor or SSRI is a type of antidepressant medication which is able to prevent nerve cells from taking back up a mood-regulating neurotransmitter called serotonin. This allows more serotonin to be available in the spaces between nerve cells where it can be used, possibly helping depression. Other SSRI's which may cause Prozac poop-out include: Zoloft (sertraline) Paxil (paroxetine) Celexa (citalopram) Lexapro (escitalopram) To read the rest of the article, click on this link to the source web page: https://www.verywell.com/what-is-prozac-poop-out-1067022 .